In a study of 18 patients receiving repetitive transcranial magnetic stimulation (rTMS), 11 patients (61%) achieved satisfactory-to-excellent pain relief—satisfactory relief (40% to 69% reduction in pain scores) was reported in 6 patients and excellent relief (pain reduction of 70% or more) was seen in 5 patients, according to a presentation by Masahito Kobayashi, MD, PhD, of the Department of Neurosurgery, Saitama Medical University, Japan, during the International Neuromodulation Society (INS) 12th World Congress, held in Montreal.1

"In my opinion, stroke patients with preserved sensory system will have better effects with rTMS," Dr. Kobayashi told Practical Pain Management. "Patients with severe stroke-caused dysesthesia, such as numbness, prickling, or uncomfortable sensations, may not be good candidates," he added—suggesting possible neural circuit damage was inhibiting response to treatment.

All stroke patients received rTMS to their primary motor cortex once a week for at least 12 weeks. Pain relief was sustained in 6 patients who continued treatment for 1 year. When treatment was stopped, the pain did not return immediately, but rather, "the pain returned gradually and slowly," said Dr. Kobayashi.

The Food and Drug Administration has approved rTMS therapy for the treatment of migraine headaches and depression. The methodology has been used off-label, and patients who have neuropathic pain after peripheral nerve injury may also be good candidates for rTMS, noted Dr. Kobayashi.

Study Design

The study participants had all been treated medically after a blood clot or bleed in one side of the brain (unilateral ischemic or hemorrhagic stroke). Several weeks into their recovery, they had begun to experience severe hand or leg pain as a consequence of brain damage from the stroke. Such central post-stroke pain can be extremely disabling and difficult to treat, impacting general functioning, mood, and overall quality of life, noted Dr. Kabayashi.

Since the 1990s, Japan has been an active center of research into the study of electrical motor cortex stimulation (EMCS) to treat post-stroke pain using surgically implanted devices. The current study builds on observations that electrical motor cortex stimulation’s effectiveness in relieving central post-stroke pain can be predicted by rTMS, suggesting the techniques share similar pain-relief mechanisms.

However, Dr. Kobayashi and colleagues from the Department of Neurology, Institute of Brain and Blood Vessels, Mihara Memorial Hospital in Saitama, Japan, point out in their peer-reviewed online publication of this study, (Neuromodulation: Technology at the Neural Interface: April 23, 2015) that there has still been controversy about the efficacy of rTMS in post-stroke pain.2 Dr. Kobayashi said in comparison to EMCS, his impression is rTMS efficacy seemed almost the same, without requiring surgery.

In 2014, a review suggested that there is probable efficacy (a level A recommendation) for short-term rTMS treatment of neuropathic pain, including central post-stroke pain, but did not speak to long-term efficacy.3

Since pain relief from rTMS increases a few days after treatment, weekly treatment sessions were selected to try to sustain pain relief at treatment intervals that could be maintained on an outpatient basis.

Low Side-Effect Profile

None of the 18 patients reported any serious side effects from weekly sessions of 10 trains of 10-second 5Hz rTMS, at 90% of the active motor threshold. Two patients reported transient, slight scalp discomfort after rTMS.

In addition to the potential of rTMS in pain relief, there has been growing research into noninvasive stimulation to augment progress in physical rehabilitation soon after stroke. It is believed that the stimulation aids in plasticity, the ability of the brain to gradually form new neural connections to take on functions previously performed by damaged areas.

A first phase of the study assessed whether rTMS had a treatment effect on pain. In it, the research team randomly assigned six patients to receive either sham or active rTMS one week and the other treatment the next, measuring pain scores before and after each session.

Once that phase had shown that rTMS did reduce the patients’ pain, an open-label treatment phase began. In this second phase, the 18 patients underwent 12 weekly rTMS sessions. The patients’ pain scores were measured just before each weekly session.

Data were collected for eight years, ending in 2014. Kobayashi said that some patients really hoped to continue rTMS after the study because their pain worsened after rTMS treatment sessions were over, and almost all the patients said that after the study ended, their pain increased to the level before rTMS.

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